Caldwell's large animal toxins

when working up a toxin case what populations do you want to look at

• all species on farm

• adult and young animal groups

how to differentiate central vs peripheral blindness

• Central (visual cortex lesion): blindness with PLR (most toxicosis)

• Peripheral (optic chiasm lesion): no opposite PLR

what are 4 diseases to think of with muscle fasciculations

• Hypocalcemia stage 1 (milk fever)

• Insecticide toxicity

• WNV horses – facial tremors

• listeria goat

cerebellar signs of large animals

• CN 8: vestibulocochlear → nystagmus and head tilt

• Intention tremor (↓fine motor control)

• Ataxia, wide base stance

why might cows eat sand

soothe abomasal ulcer

Achromotrichia definition

• speckled lightening of fur coat (red brown color instead of black)

• Copper or sulfur toxicosis

photosensitization is a sign of what underlying problem

liver disease

what type of cardiogenic edema do cows vs horses get

• cows - brisket edema

• horses -ventral tummy edema

contraindication to providing supp O2

paraquat tox

drugs to control seizures

• Diazepam

• Phenobarbital

• Propofol

• Inhalant anesthesia

• Often use: xylazine

contraindication to using dawn dish soap as derm scrub

do NOT use on sticky items - vegetable oil, peanut butter, mayo instead

contraindication to gastric lavage/decontamination

• if worried that substance will do more damage on the way up

2 absorbants used in large animal

• AC

• kaopectate

3 types of cathartics/laxatives

• Bulk – psyllium hydrophilic mucilloid (Metamucil) swells with intestinal contents to increase peristalsis when contact water

• Osmotics – MgSO4 (Epson salt), MgOH, NaSO4, DSS (horses) – draw water into the GI tract

• Lubricants – mineral oil (horses) – lubricates fecal contents and reduces water absorption

what is one thing always keep in mind when administering drugs and treating large animals

withdrawal times!

mycotoxins where found

moldy cereal grains or forage - warm temperature and high moisture

5 plant stressors

• drought

• flood 

• extreme temperatures

• insects

• herbicide damage

what species sensitive to mycotoxins

monogastrics

• ruminants are kinda resistant

mycotoxicosis vs mycosis

• mycotoxicosis - disease caused by mycotoxin exposure

• mycosis - disease from fungal infxn

what are 9 mycotoxins we have to know

• aflatoxin

• ergot alkaloids

• vomitoxin (DON)

• zeralenone

• fumonisins

• ochratoxins

• tremorgens grass staggers

aflatoxins reside in what plant

In the seeds/kernels of nuts and grains

• corn

• cottonseed

• peanuts

• cereal grains

Toxic component of aflatoxin

hepatotoxin

• B1 is the most common

pathophys of aflatoxin

1. eat it

2. direct damage to proteins, enzymes, DNA of hepatocytes

3. cellular necrosis, immune suppression, mutagenesis and neoplasm

what species most sensitive to aflatoxins

poultry, young piglets, growing animals and high producing (young and monogastric)

CS of aflatoxins

Acute

• Sudden Death

• Prolonged prothrombin time

• Hemorrhage

• Petechiation

• Bloody diarrhea

• Anorexia

• Rumen atony

• Ataxia

• Tremors

• Abortion

• Liver failure (Icterus)

Chronic/vague

• Poor growth

• Poor milk production (damaged proteins)

• Poor feed conversion (damaged proteins

• Rough coats

• Ill thrift

• Immunosuppression

• Hepatic fibrosis

• Infertility

• Carcinogenesis

production animals DO NOT produce with damaged livers

what mycotoxin caused this light and big liver

aflatoxin - poultry

what mycotoxin caused this liver pathology

aflatoxin - focal hemorrhages

what mycotoxin did this cow die of

aflatoxin - nutmeg liver, yellow, mottled

dx aflatoxin

• MDB

• CBC

• chem- liver failure

• high leakage enzymes

• sample the feed

• tissue biopsy - kidney, liver

• corn glows under blacklight sometimes

Tx aflatoxin

• remove contaminated feeds

• supplement with trace minerals and free radical scavengers (Vit E and Se)

• fix storage and clean grain

• ammoniation of feed to reduce fungal colonization

• adding binders to TMR

ergot alkaloids affect what plant

fescue and cereal grains (rye, oats, wheat, triticale)

toxic components ergot alkaloids

• Endophyte ergovaline

• Claviceps purpurea

what are 3 pathologies associated with ergot alkaloids

• vasoconstriction

• hypoPRL

• fat necrosis

pathophys for vasoconstriction, hypoPRL, fat necrosis

Pathophys vasoconstriction

• EAs activate α1 – adrenergic and serotonin receptors  (VC arteries)

• inhibit D1-dopamine receptors (block VD)

• =vasoconstriction of small vessels and poor peripheral blood flow

• exacerbated by cold weather = ischemia and necrosis

• hot weather =  can’t dissipate heat normally (cannot move blood to periphery to cool)

Pathophys hypoprolactemia (low Prl)

• Ergovaline induces overstimulation of D2-dopaminergic neurons (hypothalamus)

• Excess dopamine inhibits production and release of Prl (esp mares)

• =↓Prl = agalactia, prolonged gestation, altered placental physio

• Prolonged gestation = big foal = dystocia = no colostrum

Pathophys fat necrosis

• Mature animals

• Unknown pathopys —> Vasoconstrictive necrosis is suspected

• Soaponification of fat

  • Pendulous mass in mares —> entrap SI

  • Hard mass mesentery of cow

what mycotoxin causes this

ergot alkaloids

Hot weather CS of ergot alkaloids

aka summer slump

• hyperthermia

• Open-mouthed breathing

• Lethargy

• Unwillingness to graze → robs calves of rapid growth (poor hair coat, ↓shed)

• Poor milk production/performance

• Poor growth rates

• Infertility/can’t stay preg

Cold weather CS of ergot alkaloids

aka frost bite - Vasoconstriction

• Sloughing feet, ear tips, tails, teats

• Swelling and erythema of affected tissues

• Lameness – coronary bands

• Mastitis

• Hippo cows – no tips of ears (frostbite)

what CS does ergot alkaloids do in mares

• prolonged gestation

• dystocia

• agalactia

dx ergot alkaloids

sample the feed at various depths of hay

Tx ergot alkaloids

• remove suspect feed, clip seed heads and avoid excess fertilization

  • can use endophyte free fescue but will get infected eventually

  • only feed cleaned grains

• ammoniate hay - reduce ergovaline conc.

• supportive care -protect from heat/cold

• antibiotics for secondary infections

• domperidone within last 30-60 day gestation - cure hypoPRL

• breed cow that are raised with it as they are more tolerant

what plant does vomitoxin/DON (Deoxynivalenol) live in

corn, wheat, barley in cool, wet and delayed harvest conditions

what species is susceptible to vomitoxin

swine > ruminants

pathophys of vomitoxin

• stimulate CRTZ in medulla oblongata

• inhibit protein synthesis - poor production and/or immunosuppression

CS of vomitoxin

• Emesis

• Diarrhea

• Feed refusal

• ↓feed uptake

• Impaired nutrient absorption

• Poor production

• Clin Path abnormalities reflect excessive vomiting: ↓ Na and K,

• dehydration, metabolic alkalosis  (throw up HCl → ↓Cl alkalosis)

dx vomitoxin

detection in feed

tx vomitoxin

• remove DON and provide supportive care

• properly storage conditions + add binders to feed

Zeralenone toxin grows in what plants

corn and other grains cooler conditions than DON

what species most sensitive to zeralenone

swine - delayed detox and enterohepatic recirc.

pathophys of zeralenone

• estrogenic compound

• dairy cow -delayed estrous, swollen vulva

• often used as growth implant in steers to improve rate of gain

CS of zeralenone

Hyperestrogenism

• Swollen vulva and mammary glands

• Prolapsed rectum (repeat tenesmus)

• Overdeveloped reproductive tracts

• Nymphomania (heat, humping gilts)

• Pseudopregnancy (fluid)

• Early embryonic death (infertility) in older sows

• ↓litter size (8-10 when normally 12-18)

• Estrogenization of males – ↓ testicular weight, ridden by other males

• +/- V+ if DON toxin also involved

Tx of zeralenone

• same as DON

• remove offending feed

• add binders to feed

Fumonisins like to grow in what plant

corn with broken kernels

pathophys of fumonisins

• block sphingosine to become sphingosine lipid

• blocks lipid rich cell membrane on neurons, myocardial, hepatocytes

• = liquifactive necrosis of neurons - chronic exposure

• = myocardial necrosis - PIGS

• = direct hepatotoxicity - acute high exposure

• = equine leukoencephalomalacia - white matter of cerebrum necrosis 

CS of fumonisins

ELEM

• Rapidly fatal neuro dz

• CS appear at irreversible necrosis → horse die

• Altered mentation – depression to excitability → “furious rabies”

• Head pressing

• Ataxia

• Blindness

• Seizures

• Death

Porcine pul. Edema + LHF

• Damage to the left ventricle induces congestive pulmonary hypertension and edema

• Sudden death

• Dyspnea

• Cyanosis

Any species

• Icterus

• Ill thrift

• Poor Production

dx fumonisims

• necropsy

• clin path suggestive of liver failure

tx of fumonisims

• none once CS

• prevention is straight forward

ochratoxin is found in what plants

• cereal grains

• dried fruit (figs)

• coffee

• wine

• nuts/pistachios

what species are LEAST sensitive to ochratoxin

ruminants - can break down toxin

pathophys of ochratoxin

potent nephrotoxin

• damage PCT - acute renal failure

• = hyaline casts, dilated tubules, renal fibrosis

CS of ochratoxin

Acute renal failure

• Uremia – ammonia smell

• Depression

• Anorexia

• Reduced production

• Diarrhea

• Dehydration

• Anuria/oliguria

dx of ochratoxin

• based of CS and toxin detection

• Clin path of renal failure

tx ochratoxin

• like any other acute renal disease

• remove offending feed

• supportive care - fluids/plasmalyte, electrolyte correction

Tremorgenic grass stagger toxins grow in what type of plants

• perenial ryegrass

• bermuda grass

• dallisgrass

• bahia grass 

**highest concentration in the seeds** in the dry weather

what species is affected by tremorgens grass staggers

ruminants mostly

perennial ryegrass

• clumped seed head

bermuda grass

• looks like turkey foot

dallisgrass

• alternating seed heads

bahia grass 

• “peace sign”

pathophys of grass staggers

neurotoxin = stagger toxins

• stimulate GABA receptors in CNS —> impair motor neuroMSK control = tremors and incoordination

CS of grass staggers

• Generally mild

• Staggers – ataxia

• Hypermetric gait, no feed under her when walk

• Muscle fasciculation

• Head, ear, flank tremor

• Weakness

• Proprioceptive deficits

• Misadventures – lost cow cannot get out of ditch, fell of cliff

dx grass staggers

• CS and Hx

• feed or grass analysis

tx of grass staggers

• remove from offending pastures and add hay

• CS resolve in 2-3 days

• clip seed heads

where in environment would animal have access to arsenic

• old cotton farm sheds

• rotted bags of pesticides

• salt leached into env from arsenic

pathophys of arsenic tox

• disrupts cellular metabolism

• binds proteins and enzymes of krebs cycle

• cells with high metabolic demand are selectively damaged (enterocytes, myocardial, hepatocytes, renal medullary cells)

how does arsenic act as a cardiotoxin

Acute exposure: vasodilation and capillary damage

• congestion, edema, hemorrhage

Cardiotoxicity – direct damage to myocardial cells (left ventricle)

• arrhythmia, ischemia, and heart failure

CS of peracute, acute, chronic arsenic exposure

Peracute

• Sudden death

• Within min to hrs of ingestion

Acute – GI tract hit first (absorbed here)

• Colic

• V+

• Ataxia

• Weakness

• CV collapse

• Blood D+

• Death

• Blisters and edema (dermal contact exposure)

Chronic – slow low dose, think red

• Depression

• Anorexia

• Hemarthrosis: Stiff and enlarged joints

• Profuse blood D+

• Hematuria

• Fatigue

• Dyspnea

• Intense thirst

• Brick red MM

dx arsenic tox

• blood or tissue sample ASAP

  • delayed sample has decreased concentration

• necropsy - red erosions on everything

Tx arsenic tox

• prevent absorption

• removal from source

• empty stomach contents -emesis, rumenotomy

• AC

• chelators - BAL, NaThiosulfate, D-penicillamine, CaEDTA

• supportive care - fluids, pain meds, blood transfusion

copper where is it found in the env. for livestock to get exposed

soil and forage concentration (smokey mountain area)

what species is sensitive to copper tox

• sheep

• cattle and goats are less SN

• monogastrics tolerate

pathophys of copper tox

• directly damage cell membranes

• forms free radicals

• = cell necrosis

• GI signs

CS of copper tox

• acute - GI dz

  • GI irritation – acute

  • Mucosal erosions – necrosis

  • Blue-green discoloration to the bowel of lumen

  • Blood D+ - big mucosal damage

• chronic - liver dz

  • intravascular hemolysis crisis

  • sudden death - RBC no carry O2

  • anemia

  • icterus

  • HgBuria

  • ↑RR

  • hypoxia

  • acute renal failure

what heavy metal caused this

copper

dx copper tox

• serum or liver biopsy

• eval minerals/feed + water

• necropsy -liver, kidneys gun metal sheen, portwine urine

Tx copper tox

• blood transfusion

• chelators - NaThiosulfate

• ↑dietary molybdenum, sulfur, zinc

• ALWAYS check mineral label for sheep

source of fluoride tox for large animals

• soil and forages near industrial centers

• rodenticides

• toothpaste

pathophys of fluoride tox

• abnormal bone and tooth formation

  • binds with hydroxyapatite in bone

• increased periosteal rxn and cortical thickening

• teeth - soft chalky, weak enamel and dental dysplasia

CS of fluoride tox

• lameness

• abnormal hoof wear

• abnormal keratin growth

• mottled, chalky, soft enamel

• early loss of dentition with wear

dx fluoride tox

• bony lesions

• tissue or urine conc.

• rads/necropsy

what heavy metal caused this

fluoride

what heavy metal tox caused this

fluoride

Tx of fluoride tox

• early lesions may resolve with time

• dentition is permanent

• avoid excess exposure or high risk env.

• consider well water or filtered water instead of city water

source of iodine tox for large animals

• bad mineral formulations

• iatrogenic treatments from owners

• goitergenic plants - soybeans, brassicas

what are 3 iatrogenic ways that large animals get iodine tox

• Na I - treat lumpy jaw, wooden tongue, nasal granulomas

• EDDI - added to mineral in excess

• kelp supplement

pathophys of iodine tox

• insufficient dietary iodine

  • low T3/T4

  • Low feedback stimulus

  • excess TSH made —> goiter

• dietary excess

  • paradoxical suppression of T3/T4 production

  • still excess TSH —> goiter

CS of iodine tox in foals

• knot on knot head foats - congenital hypothyroid

  • mom fed excess iodine during gestation —> foal with goiter

  • 11 mo exposure

• mare concentrate iodine in milk

CS of iodinism

• Alopecia – face/head

• Scaling of skin

• Catarrhal – ropey nasal discharge

• Excess tearing

• Tachypnea

• Abortion- One case of goiter present in an aborted fetus

what heavy metal caused this

iodine

what heavy metal caused this

iodine

tx of iodine tox for foal vs livestock

Tx of congenital hypothyroid foals

• Removal of iodine supplementation, milk replacer, foals typically resolve in time (couple weeks)

• mares show no CS

• Avoid soybean and brassica based diets - Especially in pregnant mares

Tx – no specific tx for livestock - Removal of excess will relate to ↓ CS over time

• avoid excess iodine in the diet (put down supplements)